RU2752814C2 - Flow cell with flexible connection - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: invention relates to microfluid apparatuses, namely to a reagent control system. The apparatus for controlled chemical reactions with a flexible connection module is comprised of a reagent control system configured to be located in said apparatus, wherein the reagent control system is comprised of multiple reagent wells, wherein each reagent well is configured to accommodate a reagent from the multiple reagents contained in the system, wherein the reagent control system is configured to select a reagent flow from one of the multiple reagent wells; a detection module; and a flexible connection module comprising: a flexible connection comprised of a multilayer package and configured to be located in the device, wherein the flexible connection is comprised of a first flexible channel in fluid communication with the reagent control system, wherein the first flexible channel is configured for a reagent flow to be directed thereby; and a flow cell configured to be placed in the apparatus, wherein the flow cell comprises a flow channel in fluid communication with the first flexible channel, wherein the flow channel is configured to direct a reagent flow over the analytes located in the flow channel; wherein the flow cell is configured to be moved by the apparatus relative to a fixed base point in the apparatus while being coupled with the flexible connection.

EFFECT: technical result is provided possibility to move the flow cell by the apparatus relative to a fixed base point in the apparatus.

15 cl, 26 dwg

Description

Referring to related claims

[0001] This application is non-provisional and claims priority under the filing date of US Provisional Patent Application No. 62 / 671,481, filed May 15, 2018, entitled “Flexible Coupling Flow Cell,” the contents of which are incorporated herein by reference. This application also claims priority under Dutch Patent Application No. 2021147, filed June 18, 2018, entitled “Flexible Coupling Flow Cell”, the contents of which are incorporated herein by reference.

State of the art

[0002] Many devices employing microfluidic devices may include a reagent management system (RMS) configured to select reagents from a plurality of reagents and direct their flow to a flow cell, wherein the RMS and the flow cell can be rigidly coupled (i.e. connected so that the positions of the RMS and the flow cell remain substantially fixed relative to each other). For example, a reagent management system may include a plurality of reagent wells containing a variety of reagents, each reagent well being connected to a rotary switch valve. The rotary valve position is aligned with each reagent well for reagent selection. The selected reagents are then directed along a common line from the rotary valve to the inlet port of the flow cell.

[0003] Analytes, for example, DNA segments, nucleotide chains, or the like, can be located in the flow channel. Selected reagents can flow through the flow cell to perform a variety of controlled chemical reactions on the analytes. Chemical reactions can affect some of the detectable properties related to the analytes. For example, one such detectable property may be the emission of photons of light by analytes.

[0004] A detection module (eg, a visualization module) may be located within the device. The detection module is configured to scan the flow cell to detect detectable properties. Further, the device circuitry within the device can process and transmit data signals generated based on the detected properties. The data signals can then be analyzed to reveal the properties of the analytes.

[0005] However, flow cells in many instruments are very sensitive to vibrations during detection. In addition, for detecting small objects (eg, photons of light from analytes) in the flow cell, the detection module can often be positioned relative to the flow cell to within microns (eg, plus or minus 100 microns or less).

[0006] Since the ECM and the flow cell can be rigidly connected without being able to move within the instrument, the detection module is something that can be moved relative to the flow cell while it scans the flow cell. In this case, the detection module can exceed the flow cell in weight and size by several orders of magnitude. Therefore, accurate positioning of the detection unit may be difficult. In addition, the relatively large handling technique required to position the detection module can cause unintentional vibration of the flow cell. Moreover, due to the size of the detection module and related handling techniques, scanning in multiple positions over the entire area of the flow cell is costly and time consuming.

Disclosure of invention

[0007] The disclosed invention provides advantages over prototypes and alternatives by providing a flow cell fluidly coupled to a reactant management system (RMS) through a flexible connection. The flexible connection allows the flow cell to move relative to the base point on the instrument, while the RMS is stationary relative to the base point. As such, the flow cell is movable relative to the detection module of the instrument, while the detection module is also held in a fixed position relative to the base point. In addition, the absence of a rigid connection between the flow cell and the ECM allows the flow cell to be positioned relative to a fixed base point on the instrument more accurately than an ECM or detection module.

[0008] The ECM and the flow cell may be enclosed in a cartridge detachable from the device, and the flow cell may or may not be detachable from the cartridge. Alternatively, the RMS can be rigidly attached to the device, and the flow cell can be detachable from the device.

[0009] In addition, the flow cell and flexible connection can be assembled together and included in the flexible connection module. The flexible connection module can be connected to a cartridge or to an instrument. The module may or may not be designed with the possibility of detachable connection with the RMS in the cartridge or device.

[0010] Since the flow cell is much lighter and smaller than the detection module, manipulation techniques can be used to move the flow cell, which are smaller and less expensive than those that can be used to move the detection module. In addition, moving the flow cell, rather than the detection module, can reduce vibrations that can affect the detection accuracy of light photons or other types of detectable properties related to analytes located in the flow cell. In addition, the flow cell can be moved to different positions faster than the detection module can be moved to scan and detect the detected properties.

[0011] In addition, even if the detection module is movable and the flow cell is stationary relative to the base point of the instrument, the flexible connection can provide the advantage of reducing vibrations transmitted by the ECM to the flow cell. This is due to the fact that the flexible connection can damp the vibrations generated by the RMS when they are transmitted through the flexible connection.

[0012] In accordance with one or more aspects of the disclosed invention, an instrument includes a reagent management system (RMS) configured to be located within the instrument. The RMS includes a plurality of reagent wells, each reagent well being configured to receive a reagent from a plurality of reagents disposed in the system. The RMS is configured to select a reagent flow from a plurality of reagents. The flexible connection is also designed to be positioned in the device. The flexible connection includes a first flexible conduit in fluid communication with the ECM. The first flexible channel is configured to direct the flow of the reagent. The flow cell is also configured to be located in the device. The flow cell includes a flow channel in fluid communication with the first flexible channel. The flow channel is configured to direct the flow of the reagent over the analytes located in the flow channel. The flexible connection allows the flow cell to be moved by the instrument relative to a fixed reference point in the instrument.

[0013] In accordance with one or more aspects of the disclosed invention, an instrument cartridge includes a reagent management system (RMS) configured to select a reagent stream from a variety of reagents contained in the RMS. The flexible connection is designed to be positioned in the cartridge. The flexible connection includes a first flexible conduit in fluid communication with the ECM. The first flexible channel is configured to direct the flow of the reagent. The flow cell is configured to be positioned in a cartridge. The flow cell includes a flow channel in fluid communication with the first flexible channel. The flow channel is configured to direct reagent flows over the analytes located in the flow channel. When the cartridge is engaged with the instrument, the flexible connection allows the flow cell to be moved by the instrument relative to a fixed reference point in the instrument.

[0014] In accordance with one or more aspects of the disclosed invention, a flexible connection module includes a flexible connection and a flow cell. The flexible connection includes a through-hole inlet to the first channel, a through-hole outlet from the first channel, and a first flexible channel connected thereto by fluid. The through opening of the entrance to the first channel includes a hydraulic seal made with the possibility of being connected to the RMS outlet window and passing a reagent flow through itself. The flow cell includes an inlet port, an outlet port, and a flow channel configured in fluid communication therebetween. The inlet port is in fluid communication with the through hole of the outlet from the first flexible joint channel. The flow channel is configured to direct the flow of the reagent over the analytes located in the flow channel.

Brief Description of Drawings

[0015] A more complete understanding of the disclosed invention can be obtained from the following section "Implementation of the invention" in conjunction with the accompanying drawings, of which:

[0016] FIG. 1 is an example block diagram of an apparatus in accordance with aspects of the disclosed invention;

[0017] FIG. 2 is an example block diagram of a cartridge apparatus in accordance with aspects of the disclosed invention;

[0018] FIG. 3 is an example of a more detailed schematic diagram of the apparatus of FIG. 2 in accordance with aspects of the disclosed invention;

[0019] FIG. 4 is an example block diagram of the apparatus of FIG. 3 in accordance with aspects of the disclosed invention;

[0020] FIG. 5A is an example of a simplified perspective view of a flexible connection module and a portion of an ECM to which the module may be connected in accordance with aspects of the disclosed invention;

[0021] FIG. 5B is an example of a cross-sectional side view of the flexible connection module of FIG. 5A in accordance with aspects of the disclosed invention;

[0022] FIG. 6 is an exploded view of an example of a flexible joint comprising a topsheet, a backsheet, and an intermediate layer in accordance with aspects of the disclosed invention;

[0023] FIG. 7A is an example perspective view of the flexible joint of FIG. 6 in accordance with aspects of the disclosed invention;

[0024] FIG. 7B is an example of a front view of the flexible joint of FIG. 6 in accordance with aspects of the disclosed invention;

[0025] FIG. 8 is an exemplary graph of burst pressure versus wall to bore ratio in accordance with aspects of the disclosed invention;

[0026] FIG. 9A is an exemplary front view of a flexible joint with an intermediate stack of subcoats in which 50 percent by volume of the subcoats is adhesive in accordance with aspects of the disclosed invention;

[0027] FIG. 9B is an exemplary front view of a flexible joint with an intermediate stack of subcoats in which 25 percent by volume of the subcoats is adhesive in accordance with aspects of the disclosed invention;

[0028] FIG. 10 illustrates an example of a pair of force versus displacement plots for a straight flexible connection without a gap and a direct flexible connection with a gap, respectively, in accordance with aspects of the disclosed invention;

[0029] FIG. 11 illustrates an example of a pair of force versus displacement plots for a straight flexible joint and an S-shaped flexible joint, respectively, in accordance with aspects of the disclosed invention;

[0030] FIG. 12A illustrates an example of a pair of force versus displacement plots for a laser welded flexible joint and a glued flexible joint, respectively, in accordance with aspects of the disclosed invention;

[0031] FIG. 12B is an exploded perspective view of the laser welded flexible joint of FIG. 12A in accordance with aspects of the disclosed invention;

[0032] FIG. 12C is an exploded perspective view of the glued flexible joint of FIG. 12A in accordance with aspects of the disclosed invention;

[0033] FIG. 13A is a top view of an example of a stress relief member rigidly coupled to a flexible joint in which the stress relief member is an epoxy ball, in accordance with aspects of the disclosed invention;

[0034] FIG. 13B is a side view of an example of the strain relief member of FIG. 13A in accordance with aspects of the disclosed invention;

[0035] FIG. 13C is a bottom perspective view of an example of the stress relief element of FIG. 13A in accordance with aspects of the disclosed invention;

[0036] FIG. 14A is a top view of an example of a stress relief member rigidly coupled to a flexible joint in which the stress relief member is a groove, in accordance with aspects of the disclosed invention;

[0037] FIG. 14B is a side view of an example of the strain relief member of FIG. 14A in accordance with aspects of the disclosed invention;

[0038] FIG. 14C is a perspective view of an example of the stress relief element of FIG. 14A in accordance with aspects of the disclosed invention;

[0039] FIG. 15A is a top view of an example of a stress relief member rigidly coupled to a flexible joint, wherein the stress relief member is a one-piece piece with a first adhesive and a second adhesive thereon, in accordance with aspects of the disclosed invention;

[0040] FIG. 15B is a side view of an example of the strain relief member of FIG. 15A in accordance with aspects of the disclosed invention; and

[0041] FIG. 15C is a perspective view of an example of the stress relief element of FIG. 15A in accordance with aspects of the disclosed invention.

Implementation of the invention

[0042] Hereinafter, some examples will be disclosed to form a general understanding of the principles of design, operation, manufacture and application of the methods, systems and devices disclosed in the present description. One or more examples are illustrated in the accompanying drawings. It will be understood by those skilled in the art that the specific methods, systems and devices disclosed herein and illustrated in the accompanying drawings are not limiting examples, and that the scope of the present disclosure is defined solely by the claims. The features illustrated or disclosed in one example may be combined with those of other examples. Such modifications or variations are intended to be included within the scope of this disclosure.

[0043] The words "substantially", "approximately", "about", "relatively" and the like that may appear in the text of this disclosure, including in the claims, serve to denote and account for minor deviations, for example, those which are due to the spread of parameters during processing. These minor deviations also include zero deviation from a reference or parameter. For example, they can mean a tolerance of no more than ± 10%, for example, no more than ± 5%, for example, no more than ± 2%, for example, no more than ± 1%, for example, no more than ± 0.5%, for example, no more than ± 0.2 %, for example, not more than ± 0.1%, for example, not more than ± 0.05%.

[0044] FIG. 1 depicts an example block diagram of an apparatus 100 in accordance with aspects of the disclosed invention. Instrument 100 can be a sequencing instrument or other instrument that employs microfluidic devices.

[0045] The instrument 100 includes a flow cell 102 in fluid communication with a reactant management system (RMS) 104, wherein the RMS 104 and flow cell 102 are mechanically and flexibly coupled to each other via a flexible connection 106. The RMS 104 is selectable and directing the flow of a plurality of reactants 108, 109, 110, 111, 112, 114, 116,118 (here 108-118) (shown in more detail in FIG. 3) to the flow cell 102. In the context of this document, the word "flexible" and its derivatives mean the ability to roll, tilt or twist without breaking or losing functionality.

[0046] The flow cell 102 includes an inlet 120 and an outlet 122 connected to each other by a flow passage 124 (shown in more detail in FIG. 3). Analytes 140 (shown in more detail in FIG. 3), for example, DNA segments, nucleotide strings, or the like, can be located in the flow channel 124.

[0047] Selected reagents 108-118 can flow through flow channel 124 of flow cell 102 with the ability to direct their flows over analytes 140 to effect a variety of controlled chemical reactions of analytes with reagents 108-118 in a predetermined sequence. One example of a chemical reaction of a reagent with analytes in a flow cell is the delivery by the reagent of a recognizable label (eg, a fluorescently labeled nucleotide molecule or the like) with the ability to label the analytes. Next, the excitation light can be directed through the top layer of the flow cell (or any other part of the flow cell) to the analytes, resulting in the emission of photons of light from the fluorescent label on the analytes labeled with it. A detection unit 126 (eg, an imaging unit) of the instrument 100 can scan and / or detect emitted light photons during the detection process.

[0048] The detection unit 126 may or may not be configured to move relative to a fixed base point on the instrument 100 during the detection process. For example, the detection unit 126 can be moved while keeping the flow cell 102 stationary about a base point to scan the flow channel 124 for emitted light photons. Alternatively, for example, the detection module 126 may be held stationary and the flow cell 102 moved relative to the base point of the instrument to scan the flow channel 124 of the flow cell 102.

[0049] Further, the device circuitry within the device 100 may process and transmit data signals generated from the results of photon detection. The data signals can then be analyzed to reveal the properties of the analytes 140.

[0050] Although the detection module 126 is illustrated in this example as a visualization module capable of detecting light photons, other types of detection modules 126 and detection circuits may be used to detect other types of detectable properties related to analytes 140. For example, among detectable properties related to analytes 140 may include photons of light, electric charges, magnetic fields, electrochemical properties, changes in pH, or the like. Moreover, the detector module 126 may, among other things, include sensor devices that may be embedded in the flow cell 102, or installed in the device 100 outside the flow cell 100, or located in any combination of the above. Chemical reactions between reagents 108-118 and analytes 140 induce the analytes to influence the detectable properties.

[0051] In the context of this document, the expression "influence the detected properties" and its derivatives means, inter alia, cause the occurrence or change of the detected property with the possibility of detecting this occurrence or change by the detection unit 126. For example, influencing the detectable property may include: causing the emitted light photons to be emitted by the fluorescent labels labeled on the analytes 140, changing or creating an electromagnetic field, changing the pH, or the like.

[0052] The detector module 126 may be equipped with all cameras and / or sensors suitable and / or required for detecting influenced detectable properties. Alternatively, some of the sensors may be embedded in the flowcell itself with the ability to communicate between the sensors and the detection module 126.

[0053] The flexible connection 106 allows the flow cell 102 to move relative to a fixed base point 128 in the instrument 100 while holding the detection module 126 in a fixed position relative to the base point 128 to detect photons of light or other types of detectable properties. Alternatively, the flow cell 102 can be held in a fixed position and the detection module 126 can be moved relative to the base point 128 to detect detectable properties. In some embodiments, it is possible to move both the flow cell 102 and the detector module 126 relative to the base point 128. In particular, the flow channel 124 of the flow cell 102 is moved past the focal zones of the sensors and / or cameras of the detector module 126, which allows the detector module 126 to scan the flow channel. 124 for photons of light or other types of detectable properties related to analytes 140.

[0054] The flow cell 102 can be moved in any of three directions (indicated by the arrows X, Y, and Z) relative to the base point 128. In addition, the flow cell 102 can be rotatably moved about any of the axes or combination of axes (i. X, Y and Z) as rotation axes. In this example, the flowcell 102 can be moved with 6 degrees of freedom in three-dimensional space (ie, in any combination of linear movements in the X, Y, and Z directions plus any combination of rotation about the X, Y, Z axes). However, it is important to note that, regardless of the direction of movement of the flow cell 102, the flow cell 102 can be positioned in any of these three directions (i.e., the X direction, the Y direction, or the Z direction) relative to the base point 128 within a precise allowable range, for example, within plus or minus 100 microns or less.

[0055] Base point 128 can be any fixed structure or any number of stationary structures on tool 100. For example, base point 128 can be one or more mechanical registration holes or protrusions located throughout tool 100. In addition, base point 128 may be a single base point or multiple base points to which the ECM 104 and / or the flow cell 102 and / or the detection module 126 are aligned or positioned, with the individual base points 128 being coaxial to a common base point.

[0056] In the context of this document, multiple base points 128 or groups of base points 128 may be referred to as one or more register systems. In addition, as used herein, the positioning or alignment of a component such as flow cell 102, ECM 104, and / or detection module 126 with respect to the register system may be referred to as “registering” the component.

[0057] In addition, the flow cell 102 can be indirectly positioned relative to the base point 128. For example, the detection unit 126 can be positioned relative to the base point 128, and the flow cell 102 can be positioned relative to a fixed base point on the detection unit 126. Alternatively, for example, the detection unit 126 can be positioned relative to the base point 128, and then the detection unit 126 can be used to determine the position of the flow cell 102 relative to the detection unit 126.

[0058] The flow cell 102 is moved relative to the detection unit 126 for scanning and detection by the detection unit 126 for photons of light or other types of detectable properties that are affected by analytes 140 located over the region of the flow channel 124. Preferably, the flow cell 102 is at least , is an order of magnitude lighter and smaller than the detection module 126. This allows the flow cell 102 to be accurately positioned relative to the detection unit 126 using a smaller manipulation technique at a lower cost and faster than similar positioning of the detection unit 126 relative to the flow cell 102. In addition, vibration from movement of the flow cell 102 can be less than from moving the detection unit 126.

[0059] In addition, even if the detection unit 126 is movable and the flow cell 102 is fixed relative to the base point 128 of the instrument 100, the flexible connection 106 can provide the advantage of reducing vibrations transmitted to the flow cell 102 from the ECM 104. This is due to in that the flexible joint 106 separates the ECM 104 from the flow cell 102 and thus can dampen any vibrations generated by the ECM 104 that may be transmitted through the flexible joint 106.

[0060] Moreover, regardless of whether the detection module 126 is movable or stationary, flexible connection 106 provides the advantage of being able to independently register (i.e. position) the ECU 104 and flow cell 102 relative to separate registration systems (i.e. i.e. individual base points). Therefore, more accurate registering of both the CUR 104 and the flow cell 102 can be performed with respect to their respective base points.

[0061] For example, base point 128 may include a first base point for CRM 104 and a second base point for flow cell 102. As such, CRM 104 can be positioned relative to a first base point, while flow cell 102 can be positioned relative to a second base point. ... In this case, the positioning of the ECM 104 and the flow cell 102 relative to the respective first and second reference points can be performed independently of each other.

[0062] FIG. 2 depicts an example block diagram of a cartridge-based instrument in which instrument 100 includes a cartridge 130 in accordance with aspects of the disclosed invention. Cartridge 130 includes a flow cell 102, a CUR 104, and a flexible connection 106. Cartridge 130 may also be detachable from instrument 100. In addition, flow cell 102 may or may not be detachable from cartridge 130. When the cartridge 130 is engaged with the instrument 100, and the flow cell 102 is engaged with the cartridge 130, the CUR 104 is stationary relative to the base point 128 of the instrument 100, while the flow cell 100 can be moved relative to the base point 128 of the instrument 100.

[0063] As the cartridge 130 is engaged with the instrument 100, the positioning requirements (ie, register requirements) of the ECM 104 and the flow cell 102 can be significantly different. In particular, to engage the cartridge 130 with the tool 100, the positioning of the ECM 104 relative to the base point 128 may be approximately within a predetermined first allowable range. The first allowable range can be in millimeters, for example, no more than plus or minus 2 millimeters. However, during registering the flow cell 102 with respect to the detection unit 126 and / or moving it to a predetermined position in the device 100 for scanning by the detection unit 126, the positioning of the flow cell relative to the base point 128 can be performed within a second predetermined allowable range. The second allowable range can be micrometer, for example, no more than plus or minus 100 microns. As such, the first acceptable range may be at least 10 times the second acceptable range.

[0064] This is because the ECM 104 may be aligned with some mechanical components, such as valves and actuator motors, to be controlled by the instrument 100. The positioning of the flow cell 102 relative to the detection module 126 may be more accurate to enable optical scanning along the surface of the flow channel 124.

[0065] If the ECM 104 were rigidly coupled to the flow cell 102 (i.e., coupled to hold the ECM 104 and the flow cell 102 in substantially fixed positions relative to each other), then the positioning of both the ECM 104 and the flow cell 102 would be possible. would be in the smallest of these two acceptable ranges (ie, the second acceptable range for the flow cell 102). However, the flexible connection 106 allows different positioning requirements for the CUR 104 and flow cell 102 to be applied. Thus, the alignment of the CUR 104 and the flow cell 102 can be performed independently of each other according to their separate positioning requirements due to the possibility of separate alignment for engaging the cartridge 130. with the instrument 100 and positioning the flow cell 102 relative to the detection module 126.

[0066] Although in the example of FIG. 2, the cartridge-based instrument 100 is shown with the CUR 104 and flow cell 102 enclosed in a cartridge 130, in other embodiments, the instrument 100 may not include such a cartridge-based system. Instead, in some devices 100, the components of the ECM 104 can be integral with the device 100 or be rigidly mounted within its limits, while only the flow cell 102 can be configured to be detachable from the device 100. However, even in such devices 100 is not cartridge based, flexible connection 106 still provides the advantage of facilitating accurate positioning of flow cell 102 relative to detection unit 126 during the detection process.

[0067] FIG. 3 depicts an example of a more detailed schematic diagram of the cartridge-based device 100 of FIG. 2 with the cartridge 130 engaged thereto. The cartridge 130 includes a flow cell 102 and an ECU 104 connected to each other by a flexible connection 106.

[0068] the CRM includes a plurality of reagent wells 132. Each reagent well 132 is configured to receive a reagent from a plurality of reagents 108-118 located in the RHC. The RMS 104 is configured to select a reactant stream 134 from a plurality of reactants 108-118.

[0069] Reagents 108-118 can be any of several types or combinations of reagents depending on the type and sequence of chemical reactions to be performed in the flow cell. For example, reagents 108-118 can be of the following types:

• Reagents 108 and 109 can be different formulations of an inclusion mixture, which is a mixture of chemicals that allow the incorporation of fluorescently labeled nucleotides into DNA strands.

• Reagents 110 and 111 can be different compositions of the scan mixture, which is a mixture of chemicals that stabilize DNA strands during the detection process.

• Reagent 112 can be a mixture of cleavage, which is a mixture of chemicals that provide enzymatic cleavage of fluorescently labeled nucleotides from DNA strands.

• Reagents 114 and 116 can be different formulations of wash buffer, which is a mixture of wash reagents to remove active reagents from the flow cell.

• Reagent 118 can be air.

[0070] Flexible connection 106 includes a first flexible conduit 136 in fluid communication with the ECM 104 through an ECM outlet port 156. The first flexible conduit 136 is configured to direct reactant flow 134 through the inlet 120 of the flow cell 102 and into the flow conduit 124. The flexible connection 106 also includes a second flexible conduit 138 in fluid communication with the flow channel 124 through the outlet port 122 of the flow cell 102. The second flexible conduit 138 is configured to direct reactant flow 134 from flow cell 102, through ECM inlet port 158, and back to ECM 104 after reactant flow 134 has passed through flow channel 124.

[0071] Although the example in FIG. 3 illustrates flexible connection 106 to first and second flexible conduits 136, 138 for directing reagent flow to and from flow cell 102, other flexible connection configurations with any number of flexible conduits are also possible. For example, flexible joint 106 may include first and second flexible joints, wherein the first flexible joint has only one flexible conduit for directing reagent flow from the CUR 104 to the flow cell 102, and the second flexible connector has only one flexible conduit for directing reagent flow from flow cell 102 to ECM 104. Also, by way of example, flexible connection 106 may include multiple flexible channels for directing reactant flow to flow cell 102 and multiple flexible channels for directing reactant flow out of flow cell 102.

[0072] The flow cell 102 of the cartridge 130 includes a flow channel 124 in fluid communication with the first flexible channel 136 through the inlet port 120 and in fluid communication with the second flexible channel 138 through the outlet port 122. The flow channel 124 is configured to a variety of chemical reactions between different reactant streams 134 from multiple reactants 108-118 and analytes 140 located in flow channel 124. Flexible connection 106 allows flow cell 102 to move relative to fixed base point 128 in instrument 100.

[0073] Although the example in FIG. 3 illustrates a flow cell 102 with a single inlet 120 and a single outlet 122, other flow cell configurations are also possible. For example, the flow cell 102 may include multiple inlet ports 120 for receiving reactant streams from multiple flexible ducts 106. Also, by way of example, the flow cell may include multiple outlet ports 122 for directing reactant flow into multiple flexible ducts of the flexible connections 106.

[0074] Fixed base point 128 in this embodiment is a registration hole. However, base point 128 can be any number of stationary structures in instrument 100. For example, base point 128 can be a plurality of registration pins or holes located at different locations on the stationary body of instrument 100.

[0075] Cartridge 130 in this example includes a rotary valve 142 for selecting reagents 108-118. The rotary valve 142 includes an inner rotary valve housing 144. The valve body 144 includes a central window 146 and a pivot port 148 connected by a pivot bore 150. The valve body 144 is rotatable about a central port 146 to move the pivot port 148.

[0076] The plurality of reagent wells 132 containing reagents 108-118 may be located around the perimeter of the rotary valve 142 or otherwise outside of the rotary valve 142. Each reagent well 132 is in fluid communication with a corresponding well passage 152. Each well bore 152 includes a well bore port 154 for aligning a pivot port 148 of a rotary valve 142 to receive a reagent stream 134 from any reagent well 132.

[0077] When the pivot window 148 is aligned with one of the well port ports 154, a reagent flow path 134 is formed to allow reagent flow 134 to flow from the selected well 132, through the well port 152, through the rotary valve 142, along a common line 155 and out of the outlet windows 156 RMS. Reagent flow 134 then follows a first flexible conduit 136, into an inlet 120 of flow cell 102, and a flow conduit 124 where a selected reagent from a plurality of reagents 108-118 can react with analytes 140.

[0078] Unreacted reactants and / or reaction by-products may flow from the outlet port 122 of the flow cell 102 and through the second flexible conduit 138. The reactant stream 134 may then re-enter the ECM 104 through the ECM inlet port 158.

[0079] The inlet port 158 of the CRU 104 is in fluid communication with the first pinch valve 160. The first pinch valve 160 is in fluid communication with the second pinch valve 162. The first and second pinch valves 160, 162 have a resilient center that can be mechanically or pneumatically actuated act to shut off or pass reactant stream 134 through pinch valves 160, 162. In addition, although pinch valves 160, 162 are shown in this example, other types of valves may be used to perform the same function. For example, valves 160, 162 may be rotary valves.

[0080] An inline pump 164 (eg, a syringe or similar pump) is also located in the ECS 104. While the inline pump 164 may be a different type of pump, it will be referred to herein as a “syringe pump” 164. Syringe pump 164 is installed to form a T-shaped joint between the first and second pinch valves 160, 162. Both pinch valves 160, 162 are configured to be opened and closed by a device 100 to connect or disconnect the syringe pump 164 to the flow cell 102 and / or the flush tank 170.

[0081] The syringe pump 164 includes a reciprocating piston 166 disposed in a cylinder 168 with a cylinder bore 170. The cylinder bore 170 receives a piston 166 to form a piston-to-cylinder bore. The instrument 100 actuates the piston 166 to reciprocate within the cylinder bore 170 and pump reagents 108-118 from the reagent wells 132 to the waste can 172.

[0082] The instrument 100 also includes a detection unit 126 configured to detect photons of light or other types of detectable properties when a chemical reaction caused by reagents 108-118 causes the analytes 140 to influence such detectable properties. Flexible connection 106 allows the flow cell 102 to move relative to a fixed base point 128 in instrument 100, while the detection module 126 is held in a fixed position relative to base point 128 to facilitate detection of detectable properties.

[0083] Alternatively, the detection module 126 is movable relative to a fixed base point 128 while the flow cell 102 is held stationary relative to the base point 128. A substantially flexible connection 106 may allow more accurate positioning of the flow cell 102 relative to the base point 128 than in the case of a flow cell rigidly coupled to the ECM 104. In some embodiments, both the detection module 126 and the flow cell 102 may be movable relative to each other and / or the ECM 104.

[0084] In addition, the advantage of reducing vibrations transmitted to the flow cell 102 from the ECM 104 can be achieved even if the detection unit 126 is movable and the flow cell 102 is stationary relative to the base point 128. This is due to the fact that the flexible joint 106 separates the ECM 104 from the flow cell 102 and therefore can dampen vibrations generated by the ECM 104 that can be transmitted through the flexible joint 106.

[0085] In addition, since the flexible connection 106 separates the CUR 104 from the flow cell 102, the flexible connection 106 allows independent registration (i.e., positioning) of the CUR 104 and the flow cell 102 using separate registration systems (i.e., separate baselines). points). This allows both the CUR 104 and the flow cell 102 to be more accurately aligned to their respective base points.

[0086] Although in the embodiment of FIG. 3, the device 100 employs a rotary valve 142 that directs the flow of various reagents 108-118 along a common line 155 and into the flow cell 102; in other devices 100, the rotary valve 142 may not be used. For example, well channels 152 from each reagent well 132 may extend directly to one of a plurality of separate ECH outlet ports 156.

[0087] In such a case, each of the well channels 152 may include a valve (not shown) to control the flow of reagent 134 from each reagent well 132. In addition, the first flexible duct 136 may be a plurality of first flexible ducts, each capable of receiving a respective reactant stream 134 from a corresponding ECM outlet port 156. Moreover, the inlet 120 of the flow cell 102 may be a plurality of inlet ports 120 capable of receiving streams 134 of different reactants from each of the plurality of first flexible channels 136.

[0088] FIG. 4 discloses an example block diagram of the device 100 in FIG. 3. Instrument 100 includes a docking station 174 to receive cartridge 130. Various electrical and mechanical components within instrument 100 interact with cartridge 130 to control it during microfluidic analysis of a variety of chemical reactions occurring in flow cell 102.

[0089] Instrument 100 may include, but is not limited to, one or more processors 176 for executing program instructions stored in memory 178 for performing microfluidic analysis operations. The processors are electronically coupled to a rotary valve drive unit 180, a syringe pump drive unit 182, a pinch valve drive unit 184, a detection unit 126, and a movable temperature control unit 206.

[0090] The user interface 186 is configured to control and monitor the operation of the device 100 by the users. The communication interface 188 is configured to transfer data and other information between the device 100 and remote computers, networks, and the like.

[0091] The rotary valve drive assembly 180 includes a drive shaft 190 mechanically coupled to the rotary valve interface bracket 192. The rotary valve interface bracket 192 is selectively mechanically coupled to the rotary valve 142 of the cartridge 130. The rotary valve drive assembly 180 includes a rotation motor 194 and, in some embodiments, a translational motor 196. The translational motor 196 can move the drive shaft 190 in the translational direction from an engaging state of the rotary valve 142 to a disengaging state and vice versa. Rotation motor 194 controls rotation of rotary valve body 144 of rotary valve 142.

[0092] The rotary valve actuator assembly 180 also includes a position encoder 198 that monitors the position of the drive shaft 190. The encoder 198 sends position data to the processor 176.

[0093] The syringe pump drive assembly 182 comprises a syringe pump motor 200 coupled to an extension shaft 202. The syringe pump motor 200 moves the syringe pump shaft 202 from an extended position to a retracted position and vice versa to reciprocate the piston 166 within the bore 170 of the cylinder 168 in the syringe pump 164.

[0094] The pinch valve drive assembly 184 includes a group of two air motors 204 to drive the pinch valve. These two pinch valve drive motors 204 are mechanically coupled to the first or second pinch valve 160, 162, respectively. The pinch valve drive motors 204 are configured to pinch and or release the resilient central portion of the first and / or second pinch valves 160, 162 using air pressure, to pneumatically open and close the first and / or second pinch valves 160, 162. Alternatively, the pinch valve motors 204 may be electric.

[0095] Detection module 126 may include any cameras and / or detection sensors suitable and / or required for detecting emitted light photons or other types of detectable properties related to analytes 140 in flow cell 102. Further, a diagram of a device (not shown) within instrument 100 can process and transmit data signals generated from the results of radiation detection. The data signals can then be analyzed to reveal the properties of the analytes 140.

[0096] The device 100 may also include a thermal control unit 206 (or other environmental control device). Thermal control unit 206 may be configured to control the temperature of flow cell 102 during a variety of chemical reactions. In particular, the thermal control unit 206 can provide both heating and cooling of the flow cell 102, thereby allowing thermal cycling of the flow cell 102. The environmental monitor can control or regulate parameters other than temperature (eg, pressure). As disclosed in more detail in FIG. 5A and 5B, thermal control unit 206 is movable relative to base point 128 and may serve as a platform for positioning flow cell 102 thereon to move flow cell 102 relative to detection module 126.

[0097] FIG. 5A and 5B show an example of a flexible connection module 300. In particular, FIG. 5A depicts an example of a simplified perspective view of a flexible connection module 300 and a portion of the ECM 104 to which the module 300 may be connected. FIG. 5B depicts an example of a cross-sectional side view of a flexible connection module 300 fluidly coupled to said portion of the ECM 104, and is a cross-sectional side view along the first flexible conduit 136 of the flexible connection 106.

[0098] The flexible connection module 300 includes a flexible connection 106, a flow cell 102 and a support 302. The flexible connection 106 is mounted in fluid communication with the flow cell 102, with the support 302 serving as a frame and support for the flexible connection 106 and flow cell 102 assembly. The flexible connection module 300 may be coupled to the ECU 104 within the instrument 100 or cartridge 130.

[0099] The flexible connection 106 of the flexible connection module 300 includes a first conduit through-hole 304, a first conduit through-hole 306, and a first flexible conduit 136 in fluid communication therebetween. The first flexible channel 136 is configured to direct the flow 134 of the reactant from the outlet port 156 of the ECU 104 to the inlet port 120 of the flow cell 102.

[00100] Flexible connection 106 also includes a second conduit entry through-hole 308, a second conduit through-hole 310, and a second flexible conduit 138 in fluid communication therebetween. The second flexible channel 138 is configured to direct the flow 134 of the reactant from the outlet port 122 of the flow cell 102 to the inlet port 158 of the ECU 104.

[00101] Both the through hole 304 of the entrance to the first channel and the through hole 310 of the exit from the second channel may comprise a hydraulic seal 312. The hydraulic seal 312 of the through hole 304 of the entrance to the first channel is configured to form a connection with the outlet port 156 of the ECU 104 and pass the flow 134 of the reactant with the possibility of passage of the flow 134 of the reactant from the CUR 104 into the first flexible channel 136. The hydraulic seal 312 of the through hole 310 of the outlet from the second channel is configured to create a connection with the inlet port 158 of the CUR 104 and pass the flow 134 of the reactant with the possibility of passage of the flow 134 of the reactant from the second flexible channel 138 back to the ECM 104.

[00102] The hydraulic seals 312 in the embodiment of FIG. 5A and 5B are removable O-rings. In this case, other forms of removable hydraulic seals 312 can be used. For example, a variety of elastomeric gaskets can be used to create a removable hydraulic seal.

[00103] In addition, the hydraulic seals 312 may not be detachable to the cartridge and / or tool ECM 104. For example, the hydraulic seals 312 may be an adhesive layer bonded to the ECU 104, or the hydraulic seals 312 may be laser welded to form a permanent bond with the ECU 104.

[00104] The flow cell 102 of the flexible connection module 300 includes an inlet port 120, an outlet port 122, and a flow path 124 in fluid communication therebetween. Flow channel 124 is configured to direct reagent flow 134 over analytes 140 located in flow channel 124.

[00105] The first passage through hole 306 is in fluid communication with the inlet 120 of the flow cell 102. In addition, the second passage through hole 308 is fluidly connected to the outlet 122 of the flow cell 102. The fluid connections of the first passage through-hole 306 to the inlet port 120 and the second passage through-hole 308 to the outlet port 122 may be connected by a seal formed by the adhesive layer 314 (shown in more detail in FIG. 5B). The adhesive layer 314 creates a permanent connection between the first passage through-hole 306 and the inlet port 120 and between the second port through-hole 308 and the outlet port 122.

[00106] The adhesive layer 314 can be composed of several different materials capable of withstanding the conditions of use, including the temperature and pressure of the application, as well as chemically compatible with the reagents. For example, the adhesive layer 314 may be composed of an acrylic based adhesive, a silicone based adhesive, a temperature activated adhesive, a pressure activated adhesive, a light activated adhesive, an epoxy adhesive, and the like, or any combination thereof.

[00107] Alternatively, it is possible to use other types of connections to create sealed connections of the through-hole 306 of the exit from the first channel with the inlet port 120 and the through-hole 308 of the entrance to the second channel with the outlet port 122. For example, the connection of the through-holes to the windows may be laser welding. The through holes and windows can be releasably connected by means of a removable hydraulic seal such as an O-ring or an elastomeric gasket.

[00108] Although FIG. 5A and 5B illustrate an embodiment comprising a flexible connection 106 with a first channel inlet through-hole 304, a first channel outlet through-hole 306, a second channel inlet through-hole 308, and a second channel outlet through-hole 310, other flexible configurations are also possible. connections with any number of channels with any number of inlet and / or outlet through holes. For example, flexible connection 106 may serve to flow a single reactant into flow cell 102, and flexible connection 106 may contain only one through inlet opening from CUR 104 with multiple flexible channels fanning from a single through inlet opening to multiple through outlet openings into the flow cell. 102. Alternatively, flexible connection 106 may serve to flow a single reactant into flow cell 102, flexible connection 106 may include multiple flexible channels, each flexible channel having a single through-hole inlet from the CUR 104 and a single through-hole outlet into flow cell 102 Alternatively, flexible connection 106 may serve to flow one reactant from flow cell 102 to CUR 104, the flexible connection may contain only one through inlet from flow cell 102 with multiple flexible channels fanning from a single through inlet to multiple through holesoutlet to ECU 104. Flexible connection 106 can serve for the flow of one reagent from flow cell 102 to ECU 104, and flexible connection 106 may contain multiple flexible channels, each flexible channel having a single through hole inlet from flow cell 102 and a single through hole outlet to RMS 104. In additional embodiments, flexible connection 106 may serve to flow reactant into both flow cell 102 and flow cell 102 from the same end or opposite ends of flow cell 102. In such an embodiment, flexible connection 106 may contain only one an inlet through-hole with multiple flexible channels fanning from a single inlet through-hole to multiple outlet-through holes, or include a plurality of flexible channels, each flexible channel having a single inlet through-hole and a single outlet-through hole. Additional flexible joint configurations 106 may include a first flexible joint for flowing reactant into flow cell 102 and a second flexible joint for flowing reactant from flow cell 102, both of the first and second flexible joints may include inlet through holes, outlet through holes and flexible channels between them in a variety of configurations.

[00109] The support 302 of the flexible connection module 300 includes an inner ridge 316 surrounding the flow cell 102. The support 302 is configured to receive the flow cell 102 within the inner ridge 316. The support 302 may allow the flow cell 102 to move laterally in the Y direction and longitudinally in the X direction within the support 302. In addition, the support 302 can also move the flow cell 102 vertically in the Z direction relative to the support 302.

[00110] One mechanism by which the support device 302 can provide such movement in the X, Y and Z directions without exiting the flow cell 102 beyond the inner edge 316 is a plurality of support fingers 318 on the upper surface 320 and / or the lower surface 322 support device 302. Support fingers 318 may extend inwardly from inner ridge 316 and partially transversely across the top and / or bottom surface of flow cell 102. If support fingers 318 are located on top surface 320, support fingers 318 may be sized so that they are not passed over the flow path 124 of the flow cell 102 to avoid interference with the detection module 126 over the flow path 124 during the detection process. Support pins 318 can prevent the flow cell 102 and flexible joint 106 from moving substantially within or completely outside of the inner edge 316 of the support device 302 during transport of the flexible joint module 300 and / or operation of the instrument 100.

[00111] In addition, the pivots 318 can move the flow cell 102 laterally (Y direction) and longitudinally (X direction) within the inner rim 316. In some embodiments, the pivots 318 may be located on the bottom surface 322 of the pivot 302, with pivot pins 318 may be located on the top surface 320 of the support 302, and may be spaced apart to allow the flow cell 102 to move a predetermined amount vertically (Z direction) without exiting the flow cell 102 beyond the inner edge 316 support device 302.

[00112] Although the embodiment of FIG. 5A and 5B includes a support 302 with support pins 318 for holding the flow cell 102, and other configurations of support 302 are also possible. For example, support 302 may be a carrier plate that does not include support fingers 318, with the flow cell 102 may be attached to the top surface of the support 302. In addition, although FIG. 5A and 5B illustrate an embodiment with a support 302 extending the entire length of the flow cell 102 and flexible connection 106 together, in other configurations the support 302 may be formed with a flexible connection 106 extending beyond the outer perimeter of the support 302.

[00113] In use, the flexible connection module 300 may be coupled to the ECM 104 (shown in more detail in FIG. 5B) by aligning the hydraulic seals 312 axially with the ECM outlet port 156 and the ECM inlet port 158. The support 302 can then be attached to the CRS 104 so that the hydraulic seals 312 are clamped between the support 302 and the CRS 104. This can be done by any means of attachment, such as bolts, C-brackets, or many other types of fixtures. ... In additional embodiments, the hydraulic seals 312 and flexible connection module 300 may be attached by other fasteners such as snap-on connectors or the like. This attachment can be independent of the support 302.

[00114] In the illustrated embodiment, once the ECM 104 is in fluid communication with the flexible connection module 300, the flow cell 102 can be engaged with the movable thermal control assembly 206 (shown in more detail in FIG. 5B). In some embodiments, support pins 318 may be located on the bottom surface 322 of the support 302 so as to extend only partially across the bottom surface of the flow cell 102 to allow the flow cell 102 to engage with the movable thermal control assembly 206. Thus, a sufficient portion of the bottom surface of the flow cell 102 can be exposed to contact the surface of the thermal control assembly 206 for engagement with the flow cell 102. Such contact allows longitudinal and lateral movement of the flow cell 102 within the inner ridge 316 support device 302, while being in engagement with the node 206 thermal control.

[00115] The thermal control unit 206 is configured to position the flow cell 102 within a few microns relative to the vertical position of the detection unit 126 (ie, in the Z direction). In addition, the temperature control unit 206 may move the flow cell 102 in the X and / or Y directions to allow the detection unit 126 to scan the flow channel 124 of the flow cell 102 during detection.

[00116] Alternatively, even if the detection unit 126 is moved and the flow cell 102 is held stationary about the base point 128 during the scan event of the flow cell 102, the temperature control unit 206 can still accurately position the flow cell 102 relative to the detection unit 126 prior to scanning. ... This is because flexible connection 106 removes to some extent the coupling between movement of flow cell 102 and movement of ECM 104. As such, the initial starting position of flow cell 102 relative to detection module 126 prior to the scan event can be accurately maintained by moving flow cell 102. If flowcell 102 was not coupled to flexible connection 106 and would be rigidly coupled to ECM 104, then both flowcell 102 and / or portions of ECM 104 would have to be moved, which would complicate accurate positioning of flowcell 102 relative to detection module 126.

[00117] In addition, regardless of whether the detection module 126 is movable or stationary relative to the base point, the flexible connection 106 makes the ECM 104 independent of the flow cell 102. Thus, the flexible connection 106 allows independent registration (i.e., positioning ) SUR 104 and flow cell 102 using separate register systems (i.e. separate base points). As such, both the ECM 104 and the flow cell 102 can be more accurately driven to their respective base points.

[00118] FIG. 6 is an exploded view of an example of a flexible joint 106 comprising a topsheet 210, a backsheet 212, and an interlayer 214. The topsheet 210, the backsheet 212, and the interlayer 214 are bonded to each other via an adhesive 216 to form a laminate or laminate 218.

[00119] The first and second flexible channels 136, 138 are cut in the intermediate layer 214, for example, by laser cutting. Accordingly, the intermediate layer 214 defines the geometric characteristics of the flexible channels 136, 138. In particular, the intermediate layer 214 defines the wall width 220 and the width 222 (shown in more detail in FIGS. 7A and 7B) of the first and second flexible channels 136,138.

[00120] The top layer 210 forms the top 224 (shown in more detail in FIGS. 7A and 7B) of the first and second flexible channels 136, 138. The bottom layer forms the bottom 226 (shown in more detail in FIGS. 7A and 7B) of the first and second flexible channels 136, 138.

[00121] The first through hole 228 and the second through hole 230 are located in the bottom layer 212 of the flexible joint 106. The first and second through holes 228, 230 are in fluid communication with the first proximal end 232 and the first distal end 234 of the first flexible channel 136 in the intermediate layer 214. In addition, a third through hole 236 and a fourth through hole 238 are located in the bottom layer 212 of the flexible joint 106. The third and fourth through holes 236, 238 are fluidly connected to the second proximal end 240 and the distal end 242 of the second flexible channel 138 in the intermediate layer 214. Although the first, second, third and fourth through holes 228, 230, 236, 238 are shown in FIG. 6 located in the lower layer 212, one or more of them may be located in the upper layer 210 and / or both in the upper layer 210 and in the lower layer 212. In particular, the first through hole 228 and the third through hole 236 may be co-located either in the lower layer 212 or in the upper layer 210. In addition, the second through hole 230 and the fourth through hole 240 may also be co-located in either the lower layer 212 or the upper layer 210.

[00122] First through hole 228 may be coupled to outlet port 156 of ECU 104 to direct reagent flow 134 from ECU 104 into first flexible conduit 136 (thus, first through hole 228 may be considered a through hole of inlet of first flexible conduit 136). The second through hole 230 may be connected to the inlet 120 of the flow cell 102 to direct the flow 134 of the reactant from the first flexible conduit 136 to the flow channel 124 (thus, the second through hole 230 may be considered the through hole of the outlet of the first flexible conduit 136). The fourth through hole 238 may be coupled to the outlet 122 of the flow cell 102 to direct reactant flow 134 from the flow cell 102 to the second flexible conduit 138 (thus, the fourth through hole 238 may be considered a through hole of the inlet of the second flexible conduit 138). A third through hole 236 may be coupled to an inlet 158 of the ECU 104 to direct reactant flow 134 from the second flexible conduit 138 back to the ECA 104 (thus, the third through hole 236 may be considered a through hole of the outlet of the second flexible conduit 138).

[00123] Top layer 210, bottom layer 212, and intermediate layer 214 can be composed of several different materials capable of withstanding application parameters, including application temperature and pressure, and chemically compatible with reagents. For example, the top layer 210, the bottom layer 212, and the intermediate layer 214 may be composed of polyethylene terephthalate, polyimide, cycloolefin copolymer, polycarbonate, polypropylene, and the like.

[00124] In addition, carbon black may be added as an additive to materials such as polyethylene terephthalate to obtain polyethylene terephthalate or the like in black. Materials with added carbon black can have a relatively low autofluorescence index. In addition, the addition of carbon black can facilitate laser welding of the upper layer 210, the lower layer 212, and the intermediate layer 214.

[00125] The adhesive 216 can be composed of several different materials capable of withstanding the application parameters, including the temperature and pressure of the application, as well as chemically compatible with the reagents. For example, the adhesive 216 may be composed of an acrylic based adhesive, a silicone based adhesive, a temperature activated adhesive, a pressure activated adhesive, a light activated adhesive, an epoxy adhesive, and the like, or a combination thereof. Such adhesives 216 can be used to adhere to each other the top layer 210, the bottom layer 212, and the intermediate layer 214.

[00126] In addition to bonding to the topsheet 210, the backsheet 212 and the intermediate layer 214 bonded to each other with an adhesive (216), the topsheet 210, the backsheet 212, and the intermediate layer 214 can also be bonded to each other in other ways. For example, the top layer 210, the bottom layer 212, and the middle layer 214 may be bonded to each other by direct bonding methods such as thermal (fusion) bonding or laser welding. In addition, the top layer 210, the bottom layer 212, and the intermediate layer 214 may be bonded to each other using any combination of bonding or direct bonding methods.

[00127] In addition, for bonding or direct bonding methods, various types of surface preparation of the top layer 210, the bottom layer 212 and the intermediate layer 214 can be performed to increase the strength of these different types of bonding. Surface preparation types may include, for example, chemical surface preparation, plasma surface preparation, or the like.

[00128] One simplified manufacturing method for creating a flexible joint 106 may be as follows: starting by cutting the top layer 210, the bottom layer 212 and the intermediate layer 214 until a predetermined characteristic is achieved, for example, by laser cutting. The method may further comprise the steps of aligning the topsheet 210, the backsheet 212, and the intermediate layer 214 with each other and joining with only hand pressure to only stick the layers together and form the laminate 218. The laminate 218 can then be passed through a laminator for activating the adhesive 216 by applying a predetermined pressure. The laminate 218 may then be heated to a predetermined temperature (e.g., above about 50 ° C or above about 90 ° C) for a predetermined time (for example, at least about 2 hours) to complete the formation of flexible joint 106.

[00129] In addition, the manufacturing method may include special steps to reduce the number of possible air inclusions between the top layer 210, the bottom layer 212, and the intermediate layer 214 during assembly. For example, a positive pressure (e.g., about 100, 125, 150 psi or higher) or a vacuum (e.g., about -10, -12, -14 psi or less) can be applied for a predetermined time to decrease the number of possible air inclusions between the top layer 210, the bottom layer 212 and the intermediate layer 214. The process of applying pressure to reduce air inclusions may or may not be combined with high temperatures (eg, above about 50 ° C or above about 90 ° C).

[00130] Next, the bottom liner material (not shown) is removed, which may be positioned over the adhesive 216 of the bottom layer 212 to expose the adhesive 216. The flexible joint 106 is then connected to the CUR 104 and the flow cell 102 by applying the required force to the flexible joint 106 to activate adhesive 216 located on the bottom of the flexible joint 106.

[00131] FIGS. 7A and 7B are perspective views (FIG. 7A) and front views (FIG. 7B) of an example of flexible joint 106 in FIG. 6. For simplicity, in this particular example, only the first flexible conduit 136 is shown.

[00132] Top layer 210, bottom layer 212 and intermediate layer 214 are bonded together to form laminate 218. Top layer 210, bottom layer 212, and intermediate layer 214 are thin, for example, in some cases, from about 10 microns to about 1000 microns each. Therefore, the laminate 218 is flexible.

[00133] For example, the height 244 of the laminate (or flexible joint height) can range from about 30 microns to about 3000 microns. The channel height 246 is the distance between the top 224 and the bottom 226 of the first flexible channel 136. The channel height can be, for example, from about 10 microns to about 1000 microns. The channel width 222 is the distance between two opposing inner walls 248, 250. The wall width 220 can be of any suitable size, depending on the design parameters. For example, the range of wall widths 220 may be from about 250 microns to about 650 microns. As will be discussed in more detail in FIG. 8, the calculated ratio of wall width 220 to channel width 222 may be at least about 2.5.

[00134] FIG. 8 depicts an example plot 252 of burst pressure 256 versus the ratio 254 of wall width 220 to channel width 222. The ratio 254 of wall width 220 to channel width 222 is plotted along the horizontal axis of plot 252. 256 Gauge Burst Pressure (in psi (psig)) is plotted along the vertical axis. Each point 258 on the graph represents the 256 burst intersection point for a given ratio of 254. Note that 1 psi (in imperial units) is approximately 0.069 bar (in metric units).

[00135] The ratio 254 of wall width 220 to channel width 222 is a parameter that influences the burst pressure 256 of the flex conduit (eg, first or second flex conduits 136, 138) in flex joint 106. Typically, the larger the ratio 254, the higher the bursting pressure. pressure 256. In this case, the burst pressure 256 is understood to mean the pressure at which leak points will occur in the flexible conduit 136, 138.

[00136] The desired burst pressure 256 for a given application may depend on the application. At the same time, a burst pressure of 256 of at least 40 psi g. the first and second channels 136, 138 are generally adequate for most applications of reactant stream 134. Dots 258 on graph 252 indicate that with a ratio of 254 of at least about 2.5, the burst pressure of 256 may be at least about 40 psig.

[00137] FIG. 9A depicts an example of a front view of a flexible connection with an intermediate stack of sub-layers. FIG. 9A, 50 percent by volume of the subcoats is adhesive.

[00138] FIG. 9B also depicts an example of a front view of a flexible joint with an intermediate stack of sub-layers. FIG. 9B, 25 percent by volume of the subcoats is adhesive.

[00139] The flexible joints 106 in FIG. 9A and 9B comprise a top layer 210, a bottom layer 212, and an intermediate layer 214. The intermediate layer 214 is a plurality of intermediate sublayers 260 bonded together by an adhesive 262.

[00140] FIG. 9A, the volume of adhesive 262 is approximately 50 percent of the total adhesive 262, in combination with intermediate subcoats 260, which may be composed of, for example, polyimide. However, in FIG. 9B, the volume of adhesive 262 is only about 25 percent of the total adhesive 262, in combination with intermediate subcoats 260 of the same material (eg, polyimide).

[00141] The percentage of adhesive 262 (eg, pressure-sensitive adhesive) in total adhesive 262, in conjunction with interlayers 260, is also a parameter that influences burst pressure. The lower this percentage, the higher the burst pressure, as a rule. In the particular case of FIG. 9A and 9B, the two flexible bond structures 106 differ from each other only in the percentage of adhesive 262 in the total volume of adhesive 262 and intermediate subcoats 260. FIG. 9A, this percentage is 50 percent with a burst pressure of 50 psig. FIG. 9B, this ratio is 25 percent, with a burst pressure of 130 psig.

[00142] FIG. 10 depicts an example of a pair of plots 264 and 266 of force (in newtons) versus displacement (in millimeters) for a corresponding pair of straight flexible joints 106A, 106B. In graph 264, the corresponding flex connection 106A includes only the first and second flex channels 136, 138 located therein. In graph 266, the corresponding flex connection 106B includes the first and second flex channels 136, 138, and optionally includes a slot 268, located between flexible channels 136, 138.

[00143] The disconnection of the reagent control system (RMS) 104 from the flow cell 102 may be accompanied by the application of additional mechanical stress to both the RMS 104 and the flow cell 102. This is due to the fact that the RMS 104 and the flow cell 102 are movable relative to each other. by bending the flexible joint 106. There are several ways to relieve this additional stress. One way to reduce this stress (i.e., the force associated with movement or displacement of the flow cell 102 and / or flexible connection 106) is to position the slot 268 between the first and second flexible channels 136, 138.

[00144] From a comparison of graphs 264 and 266, it can be seen that the slit 268 reduces the force associated with the movement of the flexible connection 106B, compared to the force associated with the movement of the flexible connection 106A. In particular, the first distal end 263 of the flex joints 106A and 106B is fixedly fixed, and the second distal end 265 of the flex joints 106A and 106B is moved a predetermined distance (e.g., about 1 to 20 percent of the total length of the flex joint) in the X direction towards the first the distal end 263. The second distal end 265 is then moved in a direction perpendicular to the X direction (i.e., in the Y direction), and the force (in newtons) required to move a given displacement (in millimeters) in the Y direction is measured for plotting 264 and 266.

[00145] Slot 268 reduces the force (as seen in plot 266) by at least approximately 2 times the force associated with displacement of flexible joint 106A without slot 268 (as seen in plot 264). In particular, the force applied to move flexible joint 106A (and thus flow cell 102) a distance of one millimeter is greater than 0.2 Newtons without slit 268 (see graph 264), with slit 268 having a decrease in force applied to displacement of flexible joint 106B, to less than 0.1 Newton (see graph 266). In addition, the force applied to move the flexible joint 106A a distance of four millimeters is greater than 0.6 Newtons without the gap 268 (see graph 264), while in the presence of the gap 268 there is a decrease in the force applied to move the flexible joint 106B to less than 0.2 newtons (see graph 266).

[00146] FIG. 11 depicts an example of a pair of force versus displacement plots 270, 272 for a straight flexible connection 106C (plot 270) and for an S-shaped flexible connection 106D (plot 272). Another way to reduce the additional mechanical stress caused by disconnecting the ECS 104 from the flow cell 102 through the flexible joint 106 is to include the snake portion in the flexible joint 106. In this particular example, the snake portion is the S-shaped portion 274 in the flexible joint 106D structure on Figure 272.

[00147] As can be seen from a comparison of graphs 270 and 272, the S-shaped portion 274 reduces the force associated with movement of the flexible connection 106D, compared to the force associated with the movement of the flexible connection 106C. Namely, the first distal end 271 of the flexible joints 106C and 106D is fixedly fixed, while the second distal end 273 of the flexible joints 106C and 106D is moved a predetermined distance (for example, from about 1 to 20 percent of the total length of the flexible joint) in the X direction towards the first distal end 271. The second distal end 273 is then moved in a direction perpendicular to the X direction (i.e., in the Y direction), and the force (in newtons) required to move a given displacement (in millimeters) in the Y direction is measured to construct graphs 270 and 272.

[00148] The S-shaped portion 274 reduces the force (as seen in plot 272) by at least approximately 2 times the force associated with displacement of the flexible joint 106C without the S-shaped portion 274 (as seen in plot 270). In particular, the force applied to move flexible joint 106C (and thus flow cell 102) a distance of one millimeter is greater than 0.2 Newtons without S-shaped portion 274 (see graph 270), and with S-shaped portion 274 present reducing the force applied to move flexible joint 106D to less than 0.1 Newton (see graph 272). In addition, the force applied to move the flexible joint 106C at a distance of four millimeters is greater than 0.6 Newtons without the S-shaped part 274 (see graph 270), and in the presence of the S-shaped part 274 there is a decrease in the force applied to moving the flexible joint 106D, to less than 0.1 Newton (see graph 272).

[00149] H FIG. 12A, 12B, and 12C depict an example pair of force versus displacement plots 276, 278 for a laser welded flex joint 106E (graph 276 in FIG. 12A and FIG. 12B) and glued flex joint 106F (graph 278 in FIG. 12A and FIG. 12C. ). Both flexible joints 106E and 106F include an S-shaped portion 274.

[00150] Another way to reduce the additional stress caused by the disconnection of the ECU 104 from the flow cell 102 through the flexible joint 106 is through the selection of methods for creating a connection between the top layer 210, the bottom layer 212 and the intermediate layer 214. In this particular example, the only significant the difference between the flexible joint designs 106E and 106F for each of the plots 276, 278, respectively, is the manner in which the joint is created.

[00151] In particular, flexible connection 106E for line 276 is laser welded. Accordingly, as shown in an exploded perspective view in FIG. 12B, the topsheet 210, the backsheet 212, and the intermediate layer 214 of the flexible joint 106E are in direct contact with each other with no adhesive 216 between them. The flexible joint 106F for the schedule 278 is adhered. Accordingly, as shown in an exploded perspective view in FIG. 12C, topsheet 210, backsheet 212, and interlayer 214 of flexible joint 106F comprise a layer of adhesive 216 (eg, pressure sensitive adhesive) between the topsheet 210, the backsheet 212, and the interlayer 214.

[00152] As can be seen from a comparison of graphs 276 and 278, gluing reduces the force associated with movement of flexible connection 106F. Specifically, the first distal end 275 of the flex joints 106E and 106F is fixed, and the second distal end 277 of the flex joints 106E and 106F is moved a predetermined distance (e.g., about 1 to 20 percent of the total flex joint length) in the X direction towards the first the distal end 275. The second distal end 277 is then moved in a direction perpendicular to the X direction (i.e., in the Y direction) and the force (in newtons) required to move a given displacement (in millimeters) in the Y direction is measured to plot 276 and 278.

[00153] Bonding reduces the force by at least about 6 times, as seen from a comparison of plots 278 and 276 of the forces associated with the movement of flexible joint 106F made by bonding and flexible joint 106E made by laser welding. In particular, the force applied to move flexible joint 106E (and thus flow cell 102) a distance of one millimeter is greater than 0.6 Newtons if the joint is laser welded (see graph 276), while there is a decrease in force applied to move flexible joint 106F, to less than 0.1 Newton in the case of glued joint (see graph 278). In addition, the force applied to move flexible joint 106E four millimeters is greater than 0.8 Newtons when laser welded (see graph 276), while reducing the force applied to move flexible joint 106F to less than 0.1 Newtons in the case of a glued joint (see graph 278).

[00154] FIG. 13A, 13B, and 13C are examples of a top view (FIG. 13A), a side view (FIG. 13B), and a bottom perspective view (FIG. 13C) of a strain relief 400 rigidly connected to a flexible joint 106. In the particular example of FIG. ... 13A, 13B and 13C, the stress relief element 400 is formed as an epoxy ball 402.

[00155] The bond between the flexible joint 106 and the flow cell 102 can be strong enough to withstand the mechanical stresses (or mechanical force) exerted on the flexible joint 106 during movement of the flow cell 102, as well as the stresses caused by changes in temperature and pressure. This stress can cause the bond to slip between the flexible joint 106 and the flowcell 102 if the bond is not strong enough. Stress relief element 400 can help mitigate such stress.

[00156] If the stress relief member 400 is in the form of an epoxy bead 402, the epoxy bead 402 consists essentially of an epoxy composition disposed along an angle 404 at the junction of the outer boundary 406 of the flow cell 102 and the bottom surface 408 of the flexible joint 106. In the configuration of the stress relief element 400, at least a portion of the stress forces acting on the flexible joint 106 are redirected into the body of the flow cell 102 through the epoxy ball 402.

[00157] Any number of epoxies can be used, provided they have sufficient surface tension to form a single ball. For example, epoxy bead 402 may include acrylic or silicone based adhesives, or be made from a two-component UV-curable epoxy.

[00158] FIG. 14A, 14B, and 14C are a top view (FIG. 14A), a side view (FIG. 14B), and a perspective view (FIG. 14C) of an exemplary stress relief member 400 rigidly coupled to flexible joint 106, wherein the stress relief member 400 is formed in the form of a groove 410. The groove 410 is located between the flexible connection 106 and the support device 302.

[00159] The chute 410 is shown not to be in contact with the flow cell 102. In essence, the chute removes some of the stress (eg, shear forces) from the bond between the flow cell 102 and the flexible joint 106 and redirects the stress to the support 302 through the stress relief element 400 ... In other configurations, chute 410 may include positioning knobs (not shown) configured to align chute 410 with flow cell 102. Positioning knobs may not be designed to divert any significant amount of force into flow cell 102.

[00160] The chute 410 includes a discharge slot 412 located in the central part of the chute 410. The discharge slot 412 may extend across the entire width 414 of the chute 412 from the top surface 416 (i.e., the surface in contact with the flexible joint 106) to the bottom surface 418 ( i.e. the surface in contact with the support 302). The relief cutout 412 forms a shape to receive and shape the epoxy which is placed in the relief cutout 412 to bond the flexible connection 106 to the support 302.

[00161] The walls 420 of the discharge cutout 412 taper from the top surface 416 to the bottom surface 418 of the chute 410. That is, in a cross-sectional view, the discharge cutout 412 would have a trapezoidal shape with an area of the discharge cutout 412 at the top surface 416 less than the area of the discharge cutout. notch 412 at the bottom surface 418. By creating a larger area at the bottom surface 418, a larger area of epoxy is in contact with the support 302 than if the walls 420 were not tapering. The larger area of epoxy can provide a stronger bond between the support 302 and the groove 410.

[00162] Although in the example of FIG. 14A, 14B, and 14C, walls 420 are shown tapering apart, and other wall configurations are also possible. For example, the walls 420 can be tapered or the walls 420 can be vertical.

[00163] A plurality of adhesive carrier rings 422 are located around the outer edge of the upper surface 416 of the relief cutout 412. The adhesive carrier rings 422 project upward from the upper surface 416. In this example, the adhesive carrier rings 422 project upward to approximately level with the upper surface of flexible joint 106.

[00164] The adhesive carrier rings 422 allow the tension surface to be brought into contact with the adhesive carrier rings 422 so that the epoxy can pass over the top surface 416 of the spout 410. This facilitates the epoxy wrap around the flexible joint 106 to create a stronger bond between the flexible joint 106 and the epoxy within the gutter 410.

[00165] Although in this embodiment, the adhesive carrier rings 422 protrude to the level of the upper surface of the flexible joint 106, alternatively the adhesive carrier rings 422 may be configured to protrude to different levels. This is because the height of the adhesive carrier rings 422 may depend in part on the type of epoxy used to provide optimal contact surface tension for the epoxy.

[00166] Anchors (or through-holes) 424 are disposed on and / or in the groove 410 to enable automated fabrication. Particularly during manufacture, the 3-axis translator can grip the chute 410, after which the marks 424 can be viewed by the camera to properly position the chute 410 on the support 302.

[00167] The groove 410 can be made of plastic, such as polycarbonate or other plastic suitable for injection molding. Chute 410 can be formed as an injection molded part.

[00168] FIG. 15A, 15B, and 15C are top views (FIG. 15A), side views (FIG. 15B), and perspective views (FIG. 15C) of an exemplary stress relief member 400 rigidly coupled to flexible joint 106 wherein the stress relief member 400 is made in one piece 430 with a first adhesive 432, for example, a pressure sensitive adhesive, and a second adhesive 434, for example, a pressure sensitive adhesive, on it. One piece piece 430 is positioned between flexible joint 106 and support 302.

[00169] It is shown that the one-piece piece 430 with the first and second adhesives 432, 434 does not come into contact with the flow cell 102. The substantially one piece piece 430 removes some of the stress (eg, shear forces) from the flow cell 102 and redirects the stress to the support device 302 In other configurations, the one-piece 430 may include alignment knobs (not shown) used to align the one-piece 430 with the flow cell 102. The alignment knobs may not be designed to divert any significant amount of force into the flow cell 102.

[00170] The first adhesive 432 is sandwiched between the upper surface 436 (i.e., the surface closest to the flexible joint 106) of the one-piece piece 430 and the flexible joint 106. The second adhesive 434 is sandwiched between the lower surface 438 (i.e., the surface located closest to support 302) of one piece 430 and support 302. First adhesive 432, second adhesive 434 and one piece 430 form the configuration of a laminated stress relief member 400 attached to both flexible joint 106 and support 302 ...

[00171] Anchors (or through holes) 440 are disposed on one-piece piece 430 to enable automated fabrication. In particular, during manufacture, the 3-axis transfer device can grip the one-piece piece 430, after which the marks 440 can be viewed by the camera to properly position the piece piece 430 on the support device 302.

[00172] The one-piece piece 430 may be made of a plastic such as polycarbonate or other injection-molded plastic. One-piece part 430 can be formed as an injection molded part.

[00173] An embodiment of an apparatus in accordance with one or more aspects of the disclosed invention includes a reagent management system, a flexible connection, and a flow cell. The reagent control system is configured to be located in the device. The reagent management system includes multiple reagent wells. Moreover, each reagent well is configured to accommodate a reagent from a plurality of reagents located in the system. The reagent control system is configured to select a reagent flow from a plurality of reagents. The flexible connection is designed to be located in the device. The flexible connection includes a first flexible conduit in fluid communication with a reagent management system. The first flexible channel is configured to direct the flow of the reagent. The flow cell is configured to be located in the device. The flow cell includes a flow channel in fluid communication with the first flexible channel. The flow channel is configured to direct the flow of the reagent over the analytes located in the flow channel. The flexible connection allows the flow cell to be moved by the instrument relative to a fixed reference point in the instrument.

[00174] In another embodiment of the instrument, the flexible connection allows the flow cell to move relative to a fixed base point in the instrument while holding the detector module of the instrument in a fixed position relative to the base point.

[00175] In another embodiment, the device includes a cartridge. The cartridge includes a reagent management system, a flow cell, and a flexible connection between them. When the cartridge is engaged with the instrument and the flow cell is engaged with the cartridge, the reagent control system is stationary relative to the base point of the instrument, and the flow cell is movable relative to the base point of the instrument.

[00176] In another embodiment of the device, the reagent management system is located relative to the base point approximately within a predetermined first allowable range. The flow cell is located relative to the base point approximately within a predetermined second acceptable range. The first acceptable range is at least 10 times the second acceptable range.

[00177] In another embodiment of the device, the flexible connection includes a second flexible conduit in fluid communication with the flow channel of the flow cell. The second flexible channel is configured to direct the flow of the reagent from the flow cell to the reagent control system after the flow of the reagent passes through the flow channel.

[00178] In another embodiment, the flexible joint includes a slot located between the first and second flexible channels to reduce the force associated with movement of the flexible joint.

[00179] In another embodiment of the device, the flexible joint comprises a snake portion to reduce the force associated with movement of the flexible joint.

[00180] In another embodiment, the flexible joint includes: a top layer defining the top of the first flexible channel, a bottom layer defining the bottom of the first flexible channel, and an intermediate layer defining the wall width and width of the first flexible channel. The ratio of the wall width to the channel width is at least about 2.5.

[00181] In another embodiment, the instrument includes a detection module. When the reagent stream is directed over the analytes, a chemical reaction occurs between the reagent stream and the analytes. The chemical reaction prompts the analytes to influence the detectable properties related to the analytes. The detection module is configured to detect detected properties during movement of the flow cell relative to the detection module.

[00182] In another embodiment of the apparatus, the intermediate layer is a plurality of sub-layers.

[00183] In another embodiment of the device, the upper, intermediate and lower layers are bonded to each other by gluing, or by thermal bonding, or by direct bonding by laser welding.

[00184] An embodiment of a cartridge in accordance with one or more aspects of the disclosed invention includes a reagent management system, a flexible connection, and a flow cell, the reagent management system configured to select a reagent stream from a variety of reagents contained in the reagent management system. The flexible connection is designed to be positioned in the cartridge. The flexible connection includes a first flexible conduit in fluid communication with a reagent management system. The first flexible channel is configured to direct the flow of the reagent. The flow cell is configured to be positioned in a cartridge. The flow cell includes a flow channel in fluid communication with the first flexible channel. The flow channel is configured to direct reagent flows over the analytes located in the flow channel. When the cartridge is engaged with the instrument, the flexible connection allows the flow cell to be moved by the instrument relative to a fixed reference point in the instrument.

[00185] In another embodiment of the cartridge, the flexible connection includes a second flexible channel in fluid communication with the flow channel of the flow cell. The second flexible channel is configured to direct the flow of the reagent from the flow cell to the reagent control system after the flow of the reagent passes through the flow channel.

[00186] In another embodiment of the cartridge, the flexible joint includes a slit located between the first and second flexible channels to reduce the force associated with movement of the flexible joint.

[00187] In another embodiment of the cartridge, the flexible joint comprises a snake portion to reduce the force associated with movement of the flexible joint.

[00188] In another embodiment of the cartridge, the flexible joint includes: a top layer defining the top of the first flexible channel, a bottom layer defining the bottom of the first flexible channel, and an intermediate layer defining the wall width and width of the first flexible channel. The ratio of the wall width to the channel width is at least about 2.5.

[00189] An embodiment of a flexible connection module in accordance with one or more aspects of the disclosed invention includes a flexible connection and a flow cell. The flexible connection comprises a through opening of the entrance to the first channel, a through opening of the outlet from the first channel, and a first flexible channel connected to them through a fluid medium. The through opening of the entrance to the first channel includes a hydraulic seal configured to be connected to the outlet of the reagent control system and to pass a reagent flow through it. The flow cell includes an inlet port, an outlet port, and a flow channel configured in fluid communication therebetween. The inlet port is in fluid communication with the through hole of the outlet from the first flexible joint channel. The flow channel is configured to direct the flow of the reagent over the analytes located in the flow channel.

[00190] In another embodiment of a flexible connection module, the flexible connection includes a through-hole for an inlet to a second channel, a through-hole for an outlet from a second channel, and a second flexible channel configured for fluid communication therebetween. The through hole of the entrance to the second channel is in fluid communication with the outlet port of the flow cell. The through hole of the outlet from the second channel includes a hydraulic seal configured to be connected to the inlet of the reagent control system and to pass a reagent flow through it.

[00191] In another embodiment of the flexible connection module, the hydraulic seal is a removable hydraulic seal that can be detachably connected to the outlet of the reagent control system and pass a reagent flow through it.

[00192] In another embodiment of a flexible connection module, the flexible connection module includes a support device. The support device includes an inner ridge surrounding the flow cell. The support device is configured to accommodate the flow cell within the inner edge and to allow the flow cell to move laterally and longitudinally within the specified limits.

[00193] It should be understood that all combinations of the above disclosed aspects and additional ideas disclosed in more detail in this section (in the absence of mutual conflict between such ideas), are considered part of the disclosed in this application of the subject invention. In particular, all combinations of claimed subject matter set forth at the end of this disclosure are intended to form part of the subject matter disclosed herein.

[00194] Although the invention has been disclosed above with specific examples, it should be understood that numerous changes can be made without departing from the spirit and scope of the disclosed inventive ideas. Therefore, it is intended that the disclosure is not limited to the examples provided, but its full scope is defined by the text of the following claims.

Claims (62)

1. A device for controlled chemical reactions with a flexible connection module, containing: a reagent management system configured to be located in said device, wherein the reagent management system contains a plurality of reagent wells, wherein each reagent well is configured to contain a reagent from a plurality of reagents located in the system, while the reagent management system is selectable flowing a reagent from one of a plurality of reagent wells; detection module; and a flex connection module containing: flexible connection, consisting of a multilayer package and configured to be located in the device, the flexible connection comprises a first flexible channel fluidly connected to the reagent control system, and the first flexible channel is configured to direct the flow of the reagent through it; and a flow cell configured to be positioned in the instrument, the flow cell comprising a flow channel in fluid communication with the first flexible channel, the flow channel being configured to direct reagent flow over analytes located in the flow channel; wherein the flow cell is movable by the instrument relative to a fixed base point in the instrument while being coupled to a flexible connection. 2. The device of claim. 1, wherein the flow cell is movable relative to a fixed base point in the device, while the detection module is fixed in a fixed position relative to the base point. 3. The device according to claim 1, (a) which contains: a cartridge, wherein the cartridge contains a reagent control system, a flow cell, and a flexible connection; moreover, when the cartridge is engaged with the device, and the flow cell is engaged with the cartridge, the reagent control system is stationary relative to the base point of the device, and the flow cell is movable relative to the base point of the device; or (b) in which the reagent control system is located relative to the base point approximately within a predetermined first acceptable range; the flow cell is located relative to the base point approximately within a predetermined second allowable range, with the first allowable range at least 10 times the second allowable range; or (c) wherein the flexible connection comprises a second flexible conduit in fluid communication with the flow channel of the flow cell, the second flexible conduit being configured to direct reagent flow from the flow cell to the reagent control system after the reagent stream has passed through the flow cell. channel, and the optionally flexible connection comprises a slot located between the first flexible channel and the second flexible channel. 4. An apparatus according to claim 1, wherein the flexible connection comprises a snake portion. 5. The device according to claim 1, wherein the flexible connection comprises: the top layer forming the top of the first flexible channel; a bottom layer forming the bottom of the first flexible channel; and an intermediate layer defining the width of the wall and the width of the channel of the first flexible channel; moreover, the ratio of the width of the wall to the width of the channel exceeds approximately 2.5, and optionally: i) the intermediate layer is a plurality of sub-layers, or ii) the top layer, the intermediate layer and the bottom layer are bonded to each other by an adhesive method, or by a thermal bonding method, or by a direct laser welding method. 6. The device of claim. 1, which provides the possibility, when the flow of the reagent is directed through the flow channel, the implementation of a chemical reaction between the flow of the reagent and analytes, while the chemical reaction induces the analytes to influence the detected properties related to the analytes; and moreover, the detection module is configured to detect the properties to be detected. 7. The device of claim 1, comprising a stress relief element rigidly connected to a flexible joint, optionally the stress relief element being one of the following: epoxy bead, gutter or a one-piece piece with a first adhesive and a second adhesive on it. 8. Cartridge with flexible connection module, containing: a reagent management system configured to select a reagent flow from a plurality of reagents contained in the reagent management system; flexible connection module containing: a flexible connection formed from a multilayer package and containing a first flexible channel in fluid communication with the reagent control system, wherein the first flexible channel is configured to direct a reagent flow therethrough; and a flow cell containing a flow channel in fluid communication with the first flexible channel, the flow channel is configured to direct the flow of reagents over the analytes located in the flow channel; the flexible connection allows the flow cell to move relative to the reagent control system. 9. The cartridge of claim 8, wherein the flexible connection comprises a second flexible channel in fluid communication with the flow channel of the flow cell, wherein the second flexible channel is configured to direct reagent flow from the flow cell to the reactant control system after the flow the reagent will pass through the flow channel, and the optionally flexible connection comprises a slit located between the first flexible channel and the second flexible channel. 10. The cartridge according to claim 8, (a) in which the flexible joint contains a snake part, (b) in which the flexible connection contains: the top layer forming the top of the first flexible channel; a bottom layer forming the bottom of the first flexible channel; and an intermediate layer defining the width of the wall and the width of the channel of the first flexible channel; wherein the ratio of the width of the wall to the width of the channel is greater than about 2.5, or (c) which comprises a strain relief rigidly coupled to a flexible joint, optionally the strain relief being one of the following: epoxy bead, gutter or a one-piece piece with a first adhesive and a second adhesive on it. 11. Flexible connection module containing: a flexible connection formed from a multilayer package and containing a through hole for the entrance to the first channel, a through hole for the exit from the first channel and a first flexible channel connected to them through a fluid medium, and the through hole of the entrance to the first channel contains a hydraulic seal capable of being connected to the outlet the window of the reagent control system and the passage of the reagent flow through itself; and a flow cell comprising an inlet port, an outlet port, and a flow channel configured to fluidly communicate therebetween, the inlet port being fluidly coupled to a through hole exit from the first flexible joint channel, the flow channel being configured to direct flow a reagent on top of the analytes located in the flow channel; wherein the flow cell is movable by the instrument relative to a fixed base point in the instrument while being coupled to a flexible connection. 12. The flexible connection module of claim 11, wherein the flexible connection comprises: a through opening of the entrance to the second channel, a through opening of the outlet from the second channel, and a second flexible channel configured to be in fluid communication therebetween; wherein the through opening of the entrance to the second channel is in fluid communication with the outlet port of the flow cell; and moreover, the through opening of the outlet from the second channel contains a hydraulic seal made with the possibility of being connected to the inlet window of the reagent control system and passing the reagent flow through itself. 13. The module of claim. 11, in which the hydraulic seal is a removable hydraulic seal made with the possibility of detachable connection with the outlet port of the reagent control system and passing the reagent flow through it. 14. The module according to claim 11, containing: a support device comprising an inner ridge surrounding the flow cell, wherein the support device is configured to accommodate the flow cell within the inner ridge and to allow the flow cell to move laterally and longitudinally within the specified limits. 15. A flexible joint module according to claim 11, comprising a stress relief element rigidly connected to the flexible joint, optionally the stress relief element being one of the following: epoxy bead, gutter or a one-piece piece with a first adhesive and a second adhesive on it.

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